Cytokine-chemokine profiles in the hippocampus of patients with mesial temporal lobe epilepsy and hippocampal sclerosis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F22%3A00075989" target="_blank" >RIV/00159816:_____/22:00075989 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/65269705:_____/22:00075989 RIV/00216224:14110/22:00129659

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0920121122000092?via%3Dihub#" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0920121122000092?via%3Dihub#</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.eplepsyres.2022.106858" target="_blank" >10.1016/j.eplepsyres.2022.106858</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cytokine-chemokine profiles in the hippocampus of patients with mesial temporal lobe epilepsy and hippocampal sclerosis

Popis výsledku v původním jazyce

Purpose: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most common drug-resistant epilepsy. Despite major advances in epilepsy research, the epileptogenesis of the MTLE-HS is not well understood. The altered neuroimmune response is one of the pathomechanisms linked to progressive epileptogenesis in MTLE-HS, and understanding its role may help design future cures for pharmaco-resistant MTLE-HS. Here, the neuroimmune function was evaluated by the assessment of cytokine-chemokine profiles in brain samples from the hippocampus of patients with MTLE-HS. Methods: Brain samples from patients with MTLE-HS collected during epileptosurgical resection (n = 21) were compared to those obtained from autopsy controls (n = 13). The typing of HS was performed according to ILAE consensus classification, and patients were additionally sorted into subgroups based on the severity of neuronal depletion (Wyler grading system). Differences between patients with MTLE-HS with and without a history of febrile seizures were also assessed. RNA was isolated from native samples, and real-time gene expression analysis of cytokine-chemokine profiles, i.e., levels of IL-1β, IL-6, IL-10, IL-18, CCL2, CCL3, CCL4, and STAT3, was carried out by qRT-PCR methodology. Results: Upregulation of IL-1β (p = 0.001), IL-18 (p = 0.0018), CCL2 (p = 0,0377), CCL3 (p &lt; 0.001), and CCL4 (p &lt; 0.001) in MTLE-HS patients was detected when compared to the post-mortem hippocampal samples collected from autopsy controls. The STAT3 expression was higher in more severe neuronal loss and glial scaring determined by different Wyler grades in HS patients. Furthermore, cytokine-chemokine profiles were not different in MTLE-HS patients with or without febrile seizures. Conclusion: The upregulation of specific cytokines and chemokines in MTLE-HS provides evidence that the neuroinflammatory process contributes to MTLE epileptogenesis. History of febrile seizures did not alter the immune profiles. Specific immune mediators and related immune pathways represent potential therapeutic targets for seizure control and pharmacoresistancy prevention in MTLE associated with hippocampal sclerosis.

Název v anglickém jazyce

Cytokine-chemokine profiles in the hippocampus of patients with mesial temporal lobe epilepsy and hippocampal sclerosis

Popis výsledku anglicky

Purpose: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most common drug-resistant epilepsy. Despite major advances in epilepsy research, the epileptogenesis of the MTLE-HS is not well understood. The altered neuroimmune response is one of the pathomechanisms linked to progressive epileptogenesis in MTLE-HS, and understanding its role may help design future cures for pharmaco-resistant MTLE-HS. Here, the neuroimmune function was evaluated by the assessment of cytokine-chemokine profiles in brain samples from the hippocampus of patients with MTLE-HS. Methods: Brain samples from patients with MTLE-HS collected during epileptosurgical resection (n = 21) were compared to those obtained from autopsy controls (n = 13). The typing of HS was performed according to ILAE consensus classification, and patients were additionally sorted into subgroups based on the severity of neuronal depletion (Wyler grading system). Differences between patients with MTLE-HS with and without a history of febrile seizures were also assessed. RNA was isolated from native samples, and real-time gene expression analysis of cytokine-chemokine profiles, i.e., levels of IL-1β, IL-6, IL-10, IL-18, CCL2, CCL3, CCL4, and STAT3, was carried out by qRT-PCR methodology. Results: Upregulation of IL-1β (p = 0.001), IL-18 (p = 0.0018), CCL2 (p = 0,0377), CCL3 (p &lt; 0.001), and CCL4 (p &lt; 0.001) in MTLE-HS patients was detected when compared to the post-mortem hippocampal samples collected from autopsy controls. The STAT3 expression was higher in more severe neuronal loss and glial scaring determined by different Wyler grades in HS patients. Furthermore, cytokine-chemokine profiles were not different in MTLE-HS patients with or without febrile seizures. Conclusion: The upregulation of specific cytokines and chemokines in MTLE-HS provides evidence that the neuroinflammatory process contributes to MTLE epileptogenesis. History of febrile seizures did not alter the immune profiles. Specific immune mediators and related immune pathways represent potential therapeutic targets for seizure control and pharmacoresistancy prevention in MTLE associated with hippocampal sclerosis.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30210 - Clinical neurology

Projekt

<a href="/cs/project/NU21-04-00305" target="_blank" >NU21-04-00305: Analýza transkriptomu a metylace DNA u pacientů s fokální kortikální dysplázií</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Epilepsy Research

ISSN

0920-1211

e-ISSN

—

Svazek periodika

180

Číslo periodika v rámci svazku

FEB

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

106858

Kód UT WoS článku

000820113600007

EID výsledku v databázi Scopus

2-s2.0-85122637284